| First Author | Katome T | Year | 2013 |
| Journal | Cell Death Differ | Volume | 20 |
| Issue | 2 | Pages | 270-80 |
| PubMed ID | 22976835 | Mgi Jnum | J:205540 |
| Mgi Id | MGI:5545718 | Doi | 10.1038/cdd.2012.122 |
| Citation | Katome T, et al. (2013) Inhibition of ASK1-p38 pathway prevents neural cell death following optic nerve injury. Cell Death Differ 20(2):270-80 |
| abstractText | Optic nerve injury (ONI) induces retinal ganglion cell (RGC) death and optic nerve atrophy that lead to visual loss. Apoptosis signal-regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein kinase (MAPK) kinase kinase and has an important role in stress-induced RGC apoptosis. In this study, we found that ONI-induced p38 activation and RGC loss were suppressed in ASK1-deficient mice. Sequential in vivo retinal imaging revealed that post-ONI treatment with a p38 inhibitor into the eyeball was effective for RGC protection. ONI-induced monocyte chemotactic protein-1 production in RGCs and microglial accumulation around RGCs were suppressed in ASK1-deficient mice. In addition, the productions of tumor necrosis factor and inducible nitric oxide synthase in microglia were decreased when the ASK1-p38 pathway was blocked. These results suggest that ASK1 activation in both neural and glial cells is involved in neural cell death, and that pharmacological interruption of ASK1-p38 pathways could be beneficial in the treatment of ONI. |
